7. SUMMARY Specific Aims: Prevention of HIV-related cancers is a key priority for NIH-funded HIV research in 2016. This study will optimize screening strategies for human papillomavirus (HPV)-related cancers among people living with HIV (PLHIV), thus maximizing the benefits and minimizing the harms of screening. Specifically, the study will (1) compare risks of cervical precancer after normal and ASCUS cytology between women living with HIV (WLHIV) and women in the general population; (2) quantify and describe consistent patterns of normal and low/high-grade anal cytology among HIV-infected and HIV-uninfected men who have sex with men (HIV-MSM and MSM); and (3) determine whether two sequential anal cytology results better predict risk of anal precancer compared to one result among HIV-MSM and MSM. Significance: PLHIV have increased risks for HPV-related cancers. Preventing these cancers involves removing their precursors during colposcopy/anoscopy. Since not all precancers will progress to cancer, targeting the highest-risk precancers can minimize the harms of screening. In recent years, risk of cervical cancer among WLHIV has declined, but risk of anal cancer among HIV-MSM is extremely high and desperately requires an effective screening strategy. If this study's aims are achieved, then (1) WLHIV could avoid over-screening and unnecessary colposcopy; (2) repeated anal cytology could potentially eliminate the need for painful anoscopy for some MSM; and (3) sequential anal cytology could potentially be used to develop an anal cancer screening strategy with efficacy similar to cervical cancer screening. Approach: Aim 1 will calculate risks of cervical precancer among WLHIV using parametric survival models applied to data from the Women's Interagency HIV Study (WIHS), and will compare these to risks in the general population generated by meta-analyzing published studies. Aims 2 and 3 will analyze data from the Multicenter AIDS Cohort Study (MACS). Aim 2 will identify HIV-MSM and MSM with either (a) 3 consecutive normal anal cytology results or (b) 3 consecutive low- or high-grade cytology results, quantify prevalence of these patterns, and compare characteristics of men who have these patterns. Aim 3 will use parametric survival models to calculate risks of anal precancer after one or two normal cytology results and, separately, abnormal results. A bootstrap algorithm will test differences in risk after one vs. two results. Fellowship Information: This study is the dissertation for Ms. Hilary Robbins, a PhD student in the Department of Epidemiology at Johns Hopkins. Ms. Robbins has chosen one sponsor and two co-sponsors with complementary experience and expertise. Her training includes research, coursework, teaching, and mentorship to help her become a leading researcher in risk-tailored screening for infection-related cancers.